title: A novel HEXB mutation and its structural effects in juvenile Sandhoff disease.
abstract: Mutations in HEXB, encoding the beta-subunit common to hexosaminidases A and B, cause the neurodegenerative condition, Sandhoff disease. A homozygous missense HEXB mutation (p. D459A) was discovered in six patients with a rare juvenile variant: we show that this disrupts a salt bridge between aspartate D459 and arginine 505 at the subunit interface; R505 mutations are reported in late-onset Sandhoff disease. Identification of D459A contributes to diagnosis and molecular understanding of attenuated Sandhoff disease variants.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Wang
authors.forename: M B
authors.initials: MB
authors.lastname: Cachón-González
authors.forename: P E
authors.initials: PE
authors.lastname: Stein
authors.forename: R H
authors.initials: RH
authors.lastname: Lachmann
authors.forename: P C
authors.initials: PC
authors.lastname: Corry
authors.forename: J E
authors.initials: JE
authors.lastname: Wraith
authors.forename: T M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D012497:Sandhoff Disease / Q000235:genetics*; D044465:White People / Q000235:genetics; D054821:beta-Hexosaminidase beta Chain / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain